European Medicines Agency

Evaluation of Medicines for Human Use

London, 11 January 2007

Ref: EMEA/HMPC/182352/2005 Rev. 2

COMMITTEE ON HERBAL MEDICINAL PRODUCTS (HMPC)

FINAL

PROCEDURE FOR THE PREPARATION OF COMMUNITY MONOGRAPHS FOR HERBAL

MEDICINAL PRODUCTS WITH WELL-ESTABLISHED MEDICINAL USE

Discussed in March 2005

DRAFT AGREED BY ORGANISATIONAL MATTERS

DRAFTING GROUP

Agreed in May 2005

June 2005

ADOPTION BY HMPC FOR RELEASE FOR

CONSULTATION

October 2005

END OF CONSULTATION (DEADLINE FOR COMMENTS)

AGREED BY ORGANISATIONAL MATTERS DRAFTING
GROUP

Discussed in February 2006,

Agreed in June 2006
Discussed in March 2006,

ADOPTION BY HMPC

Adopted on 13 July 2006

REVISION AGREED BY ORGANISATIONAL MATTERS
DRAFTING GROUP

December 2006

ADOPTION BY HMPC

11 January 2007

KEYWORDS

Herbal medicinal products; HMPC; Community herbal monographs; wellestablished medicinal use

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EMEA 2007 Reproduction and/or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged

PROCEDURE FOR THE PREPARATION OF COMMUNITY MONOGRAPHS FOR HERBAL

MEDICINAL PRODUCTS WITH WELL-ESTABLISHED MEDICINAL USE

TABLE OF CONTENTS

1.

PURPOSE...........................................................................................................................................3

2.

SCOPE................................................................................................................................................3

3.

RESPONSIBILITIES........................................................................................................................3

4.

TEMPLATES NEEDED FOR THIS PROCEDURE.....................................................................3

5.

RELATED DOCUMENTS ...............................................................................................................3

6.

DEFINITIONS, ABBREVIATIONS AND REFERENCES ..........................................................4

7.

RECORDS..........................................................................................................................................4

8.

INSTRUCTIONS...............................................................................................................................5

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1.

Purpose

The purpose of this document including its attachments is to streamline and enable consistent preparation
of Community herbal monographs by the EMEA Committee for Herbal Medicinal Products (HMPC).
According to Article 16h(3) of Directive 2001/83/EC, as amended, the HMPC shall establish Community
monographs for herbal medicinal products with regard to the application of Article 10a) [previously
Article 10(1)(a)(ii) of the same directive], i.e. for herbal medicinal products of which the active
substance(s) has/have a well-established medicinal use.
The structure of Community monographs has been designed following the Summary of Product
Characteristics (SPC) structure, as established by Article 8(3)j of Directive 2001/83/EC. The SPC of a
medicinal product sets out the agreed position on the medicinal product as distilled during the course of
the assessment process.
The HMPC, when establishing a specific Community monograph for herbal medicinal products with
well-established medicinal use, has to review and assess the available information and documentation of
several herbal medicinal products, which contain the related herbal substance/herbal preparation, even
though a Community monograph does not correspond to a specific SPC.
2.

Scope

This procedure applies to all HMPC Rapporteurs/CoRapporteurs for the preparation of Community
monographs for herbal medicinal products with well-established medicinal use.
3.

Responsibilities

Rapporteurs/CoRapporteurs must ensure the adherence to this procedure in the preparation of a

Community monograph for herbal medicinal products with well-established medicinal use.
It is the responsibility of the HMPC secretariat and the Chairperson of the HMPC Working Party on
Community Monographs and Community List to verify that this procedure is adhered to and related
templates are used.
4.

Templates needed for this procedure

Template for a Community herbal monograph (EMEA/HMPC/107436/2005 Rev.2)

Assessment report template for the preparation of Community herbal monographs and for
inclusion of herbal substance(s), preparation(s) or combinations thereof in the Community list
(EMEA/HMPC/418902/2005)

5.

Related documents

Committee on Herbal Medicinal Products - Rules of Procedure (EMEA/HMPC/139800/2004).

Guideline on the documentation to be submitted for inclusion into the list of herbal substances,
preparations and combinations thereof (EMEA/HMPC/107399/2005)
Structure of the Community list of herbal substances, preparations and combinations thereof for
use in traditional herbal medicinal products (EMEA/HMPC/100824/2005 Rev.2)
Timetable for the establishment of a Community herbal monograph [not resulting from a referral
procedure] (EMEA/HMPC/126542/2005)
Procedure for the preparation of Community monographs for traditional herbal medicinal
products (EMEA/HMPC/182320/2005 Rev.2)

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6.

Definitions, abbreviations and references

Definitions
Community herbal monograph = document whose purpose is to provide a scientific summary of all data
available on the safety and efficacy of a herbal substance/preparation1 intended for medicinal use.
Abbreviations
CHMP Committee for Human Medicinal Products
CPMP Committee for Proprietary Medicinal Products
EMEA European Medicines Agency
EWP CHMP Efficacy Working Party
HMPC Committee on Herbal Medicinal Products
QRD Quality Review of Documents Group
QWP CHMP Quality Working Party
SPC Summary of Product Characteristics

References
The rules governing medicinal products in the European Union, Volume 1, Pharmaceutical
Legislation
The rules governing medicinal products in the European Union, Volumes 2A, 2B and 2C, Notice to
Applicants
Guideline on Summary of Product Characteristics (Notice to Applicants, Volume 2C Regulatory
guidelines)
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/c/spcguidrev1-oct2005.pdf
Product Information Templates, Human Medicinal Products. Quality Review of Documents Group
http://www.emea.europa.eu/htms/human/qrd/qrdintro.htm
Guideline on quality of herbal medicinal products/traditional herbal medicinal products
(CPMP/QWP/2819/00 Rev.1 and EMEA/CVMP/814/00 Rev.1)
Guideline on declaration of herbal substances and herbal preparations in herbal medicinal
products/traditional
herbal
medicinal
products
in
the
SPC
(EMEA/HMPC/CHMP/CVMP /287539/2005)
List of standard terms for pharmaceutical dosage forms, routes of administration and containers
used for medicines for human and veterinary use (European Pharmacopoeia, EDQM & Healthcare)
http://www.edqm.eu/site/page_590.php
Guideline on excipients in the label and package leaflet of medicinal products for human use
(Notice to Applicants, Volume 3B Safety, Environment and Information guidelines)
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-3/pdfs-en/3bc7a_200307en.pdf
Note for guidance on the investigation of drug interactions (CPMP/EWP/560/95)
Guideline2 on excipients in the dossier for application for marketing authorisation of a medicinal
product (CHMP/QWP/419/03)
Note for guidance on declaration of storage conditions in the product information of medicinal
products (CPMP/QWP/609/96 Rev.1)
7.

Records

All documents, including correspondence, will be filed at the EMEA in the corresponding master file
(paper documents) and electronic file (specific "Community monographs" folder in "HMPC" folder).
Rapporteur/CoRapporteur shall provide copies of relevant documents to the HMPC Secretariat.
1

The term herbal substance should be considered equivalent to the term herbal drug as defined in the European
Pharmacopoeia and the term herbal preparation should be considered equivalent to the term herbal drug
preparation as defined in the European Pharmacopoeia
2
Published as Note for guidance on excipients, antioxidants and antimicrobial preservatives in the dossier for
application for marketing authorisation of a medicinal product
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8.

Instructions

Transfer relevant information from the assessment report into the template for Community herbal
monograph under the respective headings.
When information is available, it must be recorded in accordance with the Guideline on Summary of
Product Characteristics.
For the title of the Community herbal monograph when referring to [herbal substance/herbal preparation],
the name should be recorded as:
botanical name of the plant according to the binomial system (genus, species, variety and
author),[comma] the plant part in Latin. Example: Valeriana officinalis L., radix.
In the case where more than one plant is used, all plant names should be mentioned. For example, the title
of a monograph on Hawthorn Leaf and Flower will be:
Community herbal monograph on Crataegus monogyna Jacq. (Lindm.), C. laevigata (Poiret) D.C. (C.
oxyacanthoides Thuill.) or their hybrids, C. pentagyna Waldst. et Kit. ex Willd., C. nigra Waldst. et Kit.,
C. azarolus L., folium cum flore
For the keywords section of the monograph, the botanical name of the plant according to the binomial
system, the Latin term for the herbal substance and the common name of the herbal substance in English
should be included.
Procedure for the preparation of Community monographs for herbal medicinal products with wellestablished medicinal use

1.

NAME OF THE MEDICINAL PRODUCT

The following standard statement should be included:

[To be specified for the individual finished product.]

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

The qualitative and quantitative declaration should be given in accordance with relevant herbal quality
guidance, in particular the Guideline on quality of herbal medicinal products (CPMP/QWP/2819/00
Rev.1 and EMEA/CVMP/814/00 Rev.1) and the Guideline on declaration of herbal substances and
herbal preparations in herbal medicinal products/traditional herbal medicinal products in the SPC
(EMEA/HMPC/ CHMP/CVMP/287539/2005).
Two footnotes shall appear in the title of the section.
The first footnote concerns the materials compliance to monograph(s) of the European Pharmacopoeia
that provide definitions of the herbal substance/herbal preparation(s), or, in its(their) absence, compliance
with monograph(s) of an official pharmacopoeia of a Member State if available. If such monograph(s)
does(do) not exist, the definition of the herbal substance/herbal preparation(s) must be added as far as
possible in analogy to the Ph. Eur. as footnotes per substance and preparation.
The following standard text for the first footnote can be used:
<The material complies with the Ph. Eur. <monograph><monographs>.>
The second footnote is a standard statement:
[The declaration of the active substance(s) for an individual finished product should be in accordance
with relevant herbal quality guidance.]
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Define the herbal substance by the botanical name according to the binomial system (genus, species,
variety and author), [comma] the plant part used in Latin, followed by, in bracket, the herbal substance
name in English.
Example: Valeriana officinalis L., radix (valerian root).

i) Herbal substance
Describe more precisely the herbal substance, especially whether fresh or dried.
For examples:
- dried, whole or fragmented bark of the stems and branches
- dried, ripe seeds

ii) Herbal preparations

Herbal preparations should be referred to in English, unless it is preferable to use the Latin
name given in the pharmacopoeia of a Member State.
The type of extracts should be specified as defined in the Ph. Eur. general monograph on
extracts (ref. 01/2005:0765); indicate the solvent or solvents used for extraction (exact or as a
range) and the ratio of the starting material to the genuine extract (DER).
For examples:
- liquid extract (1:4-12); extraction solvent: ethanol 50-80% (V/V)
- dried expressed juice (a-b:1)

3.

PHARMACEUTICAL FORM

Describe the type of dosage forms relevant for the herbal substance and/or herbal preparation(s) and
intended route of administration.
For example: Herbal substance or herbal preparations in solid or liquid dosage forms for oral use.
The following standard statement should be included:
[The pharmaceutical form should be described by the European Pharmacopoeia full standard term.]

4.

CLINICAL PARTICULARS 3

4.1

Therapeutic indications

The indication(s) should be stated clearly and concisely and should define the target disease or condition
distinguishing between treatment, prevention and diagnostic indication.
The indication(s) should define:

i) Standard statement
Herbal medicinal product"

ii)
a) to aid in the treatment of / in the relief of
b)
for the relief of symptoms of / in
3

For all studies cited, it should be stated by means of a detailed description which herbal substance(s)/herbal
preparation(s) have been used and information should be provided for each preparation separately.
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c)
d)
e)
f)
g)
h)
i)

as adjuvant in / to
as adjuvant in the symptomatic treatment of
for the symptomatic treatment of
for the treatment of
for the reduction in frequency/severity of
for the prevention of
etc. (other suitable formulation)

iii) Target disease or condition(s) to be treated

iv) Target population, where applicable

4.2 Posology and method of administration

The dosage has to be clearly specified for each method/route of administration and for each indication:
1)

For each age category, where appropriate (specify age ranges) i.e. infants, children4,
adolescents5, adults, elderly:
a) Specific dose
b) Maximum recommended single, daily and/or total dose, and
c) Dosage frequency

2)

If the herbal substance/preparation has not been studied in the paediatric population or if
there are insufficient data on which to base an approval for paediatric use, there should be a
recommendation that the medicinal product should not be used in the paediatric age group
until further data become available.

3)

Duration of use and any restriction on duration of use, if relevant.

4)

Intake of the product in relation to food intake.

5)

Dosage adjustments in specific patient groups, e.g. renal insufficiency, liver disease and
other concomitant diseases.

6)

Advice relevant for dosage adjustment e.g. from monitoring clinical symptoms and signs,
including medicinal product concentrations should be mentioned when appropriate.

7)

Interactions requiring specific dosage adjustments.

8)

Relevant instruction for correct administration/use.

9)

When relevant, the following standard statement should appear:

<If the symptoms persist during the use of the medicinal product, a doctor or a pharmacist should
be consulted.>

4
5

Between 2 and 11 years of age

Between 12 and 18 years of age
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4.3 Contraindications
Situations where the medicinal product must not be given for safety reasons.
i) Contraindications including specific patient populations.
ii) Other medicines or classes of medicines, which should be specifically avoided (i.e.
contraindicated), if applicable a cross-reference to section 4.5 should be given. In general,
patient populations not studied should be mentioned in section 4.4 unless a safety issue can be
predicted.
iii) Only if pregnancy is strictly contraindicated, should it be mentioned here. In section 4.6, a
cross-reference should be given and further information about the background be provided.
Contraindication in pregnancy should be supported by human data or by strong nonclinical data.
Hypersensitivity to the <active substance(s)>, extended to other parts of the same plant or possible crossreactions to other members of the relevant plant family or to any of the excipients, should be described.
The following standard statement should be used when no specific wording is necessary:
<Hypersensitivity to the active substance(s)>.

4.4 Special warnings and precautions for use

Conditions under which use of the medicinal product could be acceptable, provided that special
conditions for use are fulfilled.
i) In general it should appear in the following order, determined by the importance of the safety
information provided:
a) Relative contraindications
b) Special warnings
c) Precautions for use
Note that contraindications should be mentioned under section 4.3 only and should not be repeated
here.
ii) In accordance with the 'Guideline on excipients in the label and package leaflet of medicinal
products for human use' (Notice to Applicants, Volume 3B Safety, Environment and
Information guidelines), products containing alcohol should carry an appropriate warning based
on the total alcohol content. Where alcohol is part of the herbal preparation, e.g. in the case of
tinctures, the appropriate warning necessary for excipients or residues from the manufacturing
process should be included.

4.5

Interaction with other medicinal products and other forms of interaction

This section should provide information on the potential for clinically relevant interactions based on the
pharmacological properties of the medicinal product.
i) As relevant as per:
a) Guideline on SPCs (Notice to Applicants, Volume 2C Regulatory guidelines)
b) Note for guidance on the investigations of drug interactions (CPMP/EWP/560/95)

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4.6

Pregnancy and lactation

i) For examples of pregnancy and lactation statements, see6 Annexes I and III of the Guideline on
SPCs.
ii) If pregnancy is strictly contraindicated, further information about the background should be
provided. Contraindication in pregnancy should be supported by human data or by strong
nonclinical data.
The following standard statement can be used:
<In the absence of sufficient data, the use during pregnancy and lactation is not recommended.>

4.7

Effects on ability to drive and use machines

Where applicable the following standard statements should appear:

<{Herbal substance/preparation} has <no or negligible><minor or moderate><major> influence on the
ability to drive and use machines.>
<No studies on the effects on the ability to drive and use machines have been performed.>
<Not relevant.>
For herbal preparations containing alcohol, the appropriate statement in accordance with the Guideline
on excipients in the dossier for marketing authorisation of a medicinal product (CHMP/QWP/419/03)
should be included.

4.8

Undesirable effects

This section should provide comprehensive information based on all adverse reactions (ADRs). Adverse
events, without at least a suspected causal relationship, should not be included.
It should be worded in concise and specific language and should state what are the most serious and/or
most frequently occurring ADRs.
Any undesirable event warnings necessary for excipients or residues from the manufacturing process
should be included.
The expressions isolated/single cases/reports should not be used.
The use of general statement such as xxx may occur very rarely is not recommended. ADRs frequency
should be estimated from available data and frequency groupings described in the Guideline on SPCs
should be used, following the proposed convention, from very common (1/10) to not known (cannot
be estimated from the available data).
If there is no information on adverse reactions, the following statement should be included:
<None known.>
When relevant, the following standard statement should appear:
<If other adverse reactions not mentioned above occur, a doctor or a pharmacist should be consulted. >

Also published in the appendix 1 of the Guideline on risk assessment of medicinal products on human
reproduction and lactation: from data to labelling (EMEA/CHMP/203927/2005)
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4.9

Overdose

Describe acute symptoms and signs and potential sequelae of different dose levels of medicinal products
based on accidental mistakes by patients.
If there is no information on overdose, the following statement should be included:
<No case of overdose has been reported.>

5.

PHARMACOLOGICAL PROPERTIES7

5.1

Pharmacodynamic properties

i) Pharmacotherapeutic group: {group}, ATC code: {code}

ii) Mechanism of action (if known)
iii) Pharmacodynamic effects
iv) Clinical efficacy
5.2

Pharmacokinetic properties

If there is no information on pharmacokinetic properties, the following statement should be included:

<No data available.>

5.3

Preclinical safety data

Where relevant, the following standard statements can be used:

<Preclinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.>
<Preclinical effects were observed only at exposures considered sufficiently in excess of the maximum
human exposure indicating little relevance to clinical use.>
<Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to
clinical exposure levels and with possible relevance to clinical use were as follows.>

For all studies cited, it should be stated by means of a detailed description which herbal substance(s)/herbal
preparation(s) have been used and information should be provided for each preparation separately.
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6.

PHARMACEUTICAL PARTICULARS

Where relevant, include information on physical and chemical incompatibilities with other products,
special precautions for storage, special precautions for disposal or waste materials derived from such
medicinal products.
If there is no information on pharmaceutical particulars, the following statement should be included:
<Not applicable.>

7.

DATE OF COMPILATION/LAST REVISION

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